Although there is widespread recognition of a region with high stroke mortality in the southeastern United States that has persisted over the past 50 years (ie, the "stroke belt"), there is little agreement as to its underlying cause(s). Herein, we review data supporting 10 potential causes for the stroke belt, and assess: (1) the likelihood that each is the contributing factor to the excess mortality, and (2) areas of investigation where data are lacking and that require additional research efforts.